Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue (original) (raw)

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 /ig/min (Group 2, n = 5), or bradykinin, 25 /ig/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 /xg/min. They Were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n-17), to adrenal enucleation (Group 6, n = 8), to combined a-adrenergic and /3-adrenergic blockade (Group 7, n = 7), to a r adrenergic receptor blockade (Group 8, n = 8), or to a 2adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by-48 ± 3 and-36 ± 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 ± 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 ± 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals. Groups 6 to 8, which lacked either epinephrine or available c«i-adrenergic receptors, had no increase in MAP. We conclude that, while bradykinin produces a MAP fall with sharp stimulation of epinephrine release, the bradykinin antagonist raises MAP and also produces a direct adrenomedullary stimulation; its hypertensive response apparently depends on the a,-agonistic properties of epinephrine.